Genes

15 pages, 1577 KiB

Open AccessArticle

Disentangling the Genetic Landscape of Peripartum Depression: A Multi-Polygenic Machine Learning Approach on an Italian Sample

by Yasmin A. Harrington, Lidia Fortaner-Uyà, Marco Paolini, Sara Poletti, Cristina Lorenzi, Sara Spadini, Elisa M. T. Melloni, Elena Agnoletto, Raffaella Zanardi, Cristina Colombo and Francesco Benedetti

Genes 2024, 15(12), 1517; https://doi.org/10.3390/genes15121517 (registering DOI) - 26 Nov 2024

Abstract

Background: The genetic determinants of peripartum depression (PPD) are not fully understood. Using a multi-polygenic score approach, we characterized the relationship between genome-wide information and the history of PPD in patients with mood disorders, with the hypothesis that multiple polygenic risk scores (PRSs) [...] Read more.

Background: The genetic determinants of peripartum depression (PPD) are not fully understood. Using a multi-polygenic score approach, we characterized the relationship between genome-wide information and the history of PPD in patients with mood disorders, with the hypothesis that multiple polygenic risk scores (PRSs) could potentially influence the development of PPD. Methods: We calculated 341 PRSs for 178 parous mood disorder inpatients affected by major depressive disorder (MDD) or bipolar disorder (BD) with (n = 62) and without (n = 116) a history of PPD. We used partial least squares regression in a novel machine learning pipeline to rank PRSs based on their contribution to the prediction of PPD, in the whole sample and separately in the two diagnostic groups. Results: The PLS linear regression in the whole sample defined a model explaining 27.12% of the variance in the presence of PPD history, 56.73% of variance among MDD, and 42.96% of variance in BD. Our findings highlight that multiple genetic factors related to circadian rhythms, inflammation, and psychiatric diagnoses are top contributors to the prediction of PPD. Specifically, in MDD, the top contributing PRS was monocyte count, while in BD, it was chronotype, with PRSs for inflammation and psychiatric diagnoses significantly contributing to both groups. Conclusions: These results confirm previous literature about the immune system dysregulation in postpartum mood disorders, and shed light on which genetic factors are involved in the pathophysiology of PPD. Full article

(This article belongs to the Section Bioinformatics)

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16 pages, 1712 KiB

Open AccessArticle

Combined Use of Univariate and Multivariate Approaches to Detect Selection Signatures Associated with Milk or Meat Production in Cattle

by Michele Congiu, Alberto Cesarani, Laura Falchi, Nicolò Pietro Paolo Macciotta and Corrado Dimauro

Genes 2024, 15(12), 1516; https://doi.org/10.3390/genes15121516 (registering DOI) - 26 Nov 2024

Abstract

Objectives: The aim of this study was to investigate the genomic structure of the cattle breeds selected for meat and milk production and to identify selection signatures between them. Methods: A total of 391 animals genotyped at 41,258 SNPs and belonging to nine [...] Read more.

Objectives: The aim of this study was to investigate the genomic structure of the cattle breeds selected for meat and milk production and to identify selection signatures between them. Methods: A total of 391 animals genotyped at 41,258 SNPs and belonging to nine breeds were considered: Angus (N = 62), Charolais (46), Hereford (31), Limousin (44), and Piedmontese (24), clustered in the Meat group, and Brown Swiss (42), Holstein (63), Jersey (49), and Montbéliarde (30), clustered in the Milk group. The population stratification was analyzed by principal component analysis (PCA), whereas selection signatures were identified by univariate (Wright fixation index, F_ST) and multivariate (canonical discriminant analysis, CDA) approaches. Markers with F_ST values larger than three standard deviations from the chromosomal mean were considered interesting. Attention was focused on markers selected by both techniques. Results: A total of 10 SNPs located on seven different chromosomes (7, 10, 14, 16, 17, 18, and 24) were identified. Close to these SNPs (±250 kb), 165 QTL and 51 genes were found. The QTL were grouped in 45 different terms, of which three were significant (Bonferroni correction < 0.05): milk fat content, tenderness score, and length of productive life. Moreover, genes mainly associated with milk production, immunity and environmental adaptation, and reproduction were mapped close to the common SNPs. Conclusions: The results of the present study suggest that the combined use of univariate and multivariate approaches can help to better identify selection signatures due to directional selection. Full article

(This article belongs to the Section Animal Genetics and Genomics)

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14 pages, 1809 KiB

Open AccessArticle

Metachromatic Leukodystrophy in Morocco: Identification of Causative Variants by Next-Generation Sequencing (NGS)

by Miloud Hammoud, María Domínguez-Ruiz, Imane Assiri, Daniel Rodrigues, Nisrine Aboussair, Val F. Lanza, Jesús Villarrubia, Cristóbal Colón, Naima Fdil and Francisco J. del Castillo

Genes 2024, 15(12), 1515; https://doi.org/10.3390/genes15121515 (registering DOI) - 26 Nov 2024

Abstract

(1) Background: Most rare disease patients endure long delays in obtaining a correct diagnosis, the so-called “diagnostic odyssey”, due to a combination of the rarity of their disorder and the lack of awareness of rare diseases among both primary care professionals and specialists. [...] Read more.

(1) Background: Most rare disease patients endure long delays in obtaining a correct diagnosis, the so-called “diagnostic odyssey”, due to a combination of the rarity of their disorder and the lack of awareness of rare diseases among both primary care professionals and specialists. Next-generation sequencing (NGS) techniques that target genes underlying diverse phenotypic traits or groups of diseases are helping reduce these delays; (2) Methods: We used a combination of biochemical (thin-layer chromatography and high-performance liquid chromatography-tandem mass spectrometry), NGS (resequencing gene panels) and splicing assays to achieve a complete diagnosis of three patients with suspected metachromatic leukodystrophy, a neurologic lysosomal disorder; (3) Results: Affected individuals in each family were homozygotes for harmful variants in the ARSA gene, one of them novel (c.854+1dup, in family 1) and the other already described (c.640G>A, p.(Ala214Thr), in family 2). In addition, both affected individuals in family 2 were carriers of a known pathogenic variant in an additionallysosomal disease gene, GNPTAB (for mucolipidosis III). This additional variant may modify the clinical presentation by increasing lysosomal dysfunction. (4) Conclusions: We demonstrated the deleterious effect of the novel variant c.854+1dup on the splicing of ARSA transcripts. We also confirmed the involvement of variant c.640G>A in metachromatic leukodystrophy. Our results show the power of diagnostic approaches that combine deep phenotyping, NGS, and biochemical and functional techniques. Full article

(This article belongs to the Special Issue Application of Next-Generation Sequencing in Genetic Diseases Diagnosis)

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17 pages, 3387 KiB

Open AccessArticle

RNA Sequencing and Weighted Gene Co-Expression Network Analysis Highlight DNA Replication and Key Genes in Nucleolin-Depleted Hepatoblastoma Cells

by Hannes Steinkellner, Silvia Madritsch, Mara Kluge, Teresa Seipel, Victoria Sarne, Anna Huber, Markus Schosserer, Raimund Oberle, Winfried Neuhaus, Alexander V. Beribisky and Franco Laccone

Genes 2024, 15(12), 1514; https://doi.org/10.3390/genes15121514 (registering DOI) - 26 Nov 2024

Abstract

Background/objectives: Nucleolin is a major component of the nucleolus and is involved in various aspects of ribosome biogenesis. However, it is also implicated in non-nucleolar functions such as cell cycle regulation and proliferation, linking it to various pathologic processes. The aim of this [...] Read more.

Background/objectives: Nucleolin is a major component of the nucleolus and is involved in various aspects of ribosome biogenesis. However, it is also implicated in non-nucleolar functions such as cell cycle regulation and proliferation, linking it to various pathologic processes. The aim of this study was to use differential gene expression analysis and Weighted Gene Co-expression Network analysis (WGCNA) to identify nucleolin-related regulatory pathways and possible key genes as novel therapeutic targets for cancer, viral infections and other diseases. Methods: We used two different siRNAs to downregulate the expression of nucleolin in a human hepatoblastoma (HepG2) cell line. We carried out RNA-sequencing (RNA-Seq), performed enrichment analysis of the pathways of the differentially expressed genes (DEGs) and identified protein–protein interaction (PPI) networks. Results: Both siRNAs showed high knockdown efficiency in HepG2 cells, resulting in the disruption of the nucleolar architecture and the downregulation of rRNA gene expression, both downstream hallmarks of a loss of nucleolin function. RNA-Seq identified 44 robust DEGs in both siRNA cell models. The enrichment analysis of the pathways of the downregulated genes confirmed the essential role of nucleolin in DNA replication and cell cycle processes. In addition, we identified seven hub genes linked to NCL: MCM6, MCM3, FEN1, MYBL2, MSH6, CDC6 and RBM14; all are known to be implicated in DNA replication, cell cycle progression and oncogenesis. Conclusions: Our findings demonstrate the functional consequences of nucleolin depletion in HepG2 and confirm the importance of nucleolin in DNA replication and cell cycle processes. These data will further enhance our understanding of the molecular and pathologic mechanisms of nucleolin and provide new therapeutic perspectives in disease. Full article

(This article belongs to the Special Issue Bioinformatics of Human Diseases)

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21 pages, 9147 KiB

Open AccessArticle

Exploration and Enrichment Analysis of the QTLome for Important Traits in Livestock Species

by Francisco J. Jahuey-Martínez, José A. Martínez-Quintana, Felipe A. Rodríguez-Almeida and Gaspar M. Parra-Bracamonte

Genes 2024, 15(12), 1513; https://doi.org/10.3390/genes15121513 (registering DOI) - 26 Nov 2024

Abstract

Background: Quantitative trait loci (QTL) are genomic regions that influence essential traits in livestock. Understanding QTL distribution and density across species’ genomes is crucial for animal genetics research. Objectives: This study explored the QTLome of cattle, pigs, sheep, and chickens by analyzing QTL [...] Read more.

Background: Quantitative trait loci (QTL) are genomic regions that influence essential traits in livestock. Understanding QTL distribution and density across species’ genomes is crucial for animal genetics research. Objectives: This study explored the QTLome of cattle, pigs, sheep, and chickens by analyzing QTL distribution and evaluating the correlation between QTL, gene density, and chromosome size with the aim to identify QTL-enriched genomic regions. Methods: Data from 211,715 QTL (1994–2021) were retrieved from the AnimalQTLdb and analyzed using R software v4.2.1. Unique QTL annotations were identified, and redundant or inconsistent data were removed. Statistical analyses included Pearson correlations and binomial, hypergeometric, and bootstrap-based enrichment tests. Results: QTL densities per Mbp were 10 for bovine, 4 for pig, 1 for sheep, and 3 for chicken genomes. Analysis of QTL distribution across chromosomes revealed uneven patterns, with certain regions enriched for QTL. Correlation analysis revealed a strong positive relationship between QTL and gene density/chromosome size across all species (p < 0.05). Enrichment analysis identified pleiotropic regions, where QTL affect multiple traits, often aligning with known candidate and major genes. Significant QTL-enriched windows (p < 0.05) were detected, with 699 (187), 355 (68), 50 (15), and 38 (17) genomic windows for cattle, pigs, sheep, and chickens, respectively, associated with overall traits (and specific phenotypic categories). Conclusions: This study provides critical insights into QTL distribution and its correlation with gene density, offering valuable data for advancing genetic research in livestock species. The identification of QTL-enriched regions also highlights key areas for future exploration in trait improvement programs. Full article

(This article belongs to the Special Issue Functional Genomics and Breeding of Animals)

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20 pages, 1899 KiB

Open AccessArticle

B Chromosome Transcriptional Inactivation in the Spermatogenesis of the Grasshopper Eyprepocnemis plorans

by Juan Luis Santos, María Teresa Parra, Sara Arévalo, Andrea Guajardo-Grence, Jesús Page, José Ángel Suja, Carlos García de la Vega and Alberto Viera

Genes 2024, 15(12), 1512; https://doi.org/10.3390/genes15121512 (registering DOI) - 25 Nov 2024

Abstract

Background/Objectives: We analyzed the relationship between synapsis, recombination, and transcription during the spermatogenesis of the grasshopper Eyprepocnemis plorans carrying B chromosomes (type B1). Methods: The progression of synapsis was interpreted according to the dynamics of the cohesin subunit SMC3 axes. DNA double-strand breaks [...] Read more.

Background/Objectives: We analyzed the relationship between synapsis, recombination, and transcription during the spermatogenesis of the grasshopper Eyprepocnemis plorans carrying B chromosomes (type B1). Methods: The progression of synapsis was interpreted according to the dynamics of the cohesin subunit SMC3 axes. DNA double-strand breaks were revealed by RAD51 immunolabeling, while transcriptional activity was determined by the presence of RNA polymerase II phosphorylated at serine 2 (pRNApol II) immunolabeling. The two repressive epigenetic modifications, histone H3 methylated at lysine 9 (H3K9me3) and histone H2AX phosphorylated at serine 139 (γ-H2AX), were employed to reveal transcriptional inactivity. Results: During prophase I, spermatocytes with one B1 chromosome showed overall transcription except in the regions occupied by both the X and the B1 chromosomes. This transcriptional inactivity was accompanied by the accumulation of repressive epigenetic modifications. When two B1 chromosomes were present, they could appear as a fully synapsed monochiasmatic bivalent, showing intense H3K9me3 labeling and absence of pRNApol II, while γ-H2AX labeling was similar to that shown by the autosomes. Conclusions: According to our results, B1 transcriptional inactivation was triggered in spermatogonia, long before the beginning of meiosis, and was accompanied by H3K9me3 heterochromatinization that was maintained throughout spermatogenesis. Moreover, when two B1 were present, the transcriptional inactivation did not preclude synapsis and recombination achievement by these chromosomes. Full article

(This article belongs to the Section Cytogenomics)

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20 pages, 3184 KiB

Open AccessArticle

GATv2EPI: Predicting Enhancer–Promoter Interactions with a Dynamic Graph Attention Network

by Tianjiao Zhang, Xingjie Zhao, Hao Sun, Bo Gao and Xiaoqi Liu

Genes 2024, 15(12), 1511; https://doi.org/10.3390/genes15121511 - 25 Nov 2024

Abstract

Background: The enhancer–promoter interaction (EPI) is a critical component of gene regulatory networks, playing a significant role in understanding the complexity of gene expression. Traditional EPI prediction methods focus on one-to-one interactions, neglecting more complex one-to-many and many-to-many patterns. To address this gap, [...] Read more.

Background: The enhancer–promoter interaction (EPI) is a critical component of gene regulatory networks, playing a significant role in understanding the complexity of gene expression. Traditional EPI prediction methods focus on one-to-one interactions, neglecting more complex one-to-many and many-to-many patterns. To address this gap, we utilize graph neural networks to comprehensively explore all interaction patterns between enhancers and promoters, capturing complex regulatory relationships for more accurate predictions. Methods: In this study, we introduce a novel EPI prediction framework, GATv2EPI, based on dynamic graph attention neural networks. GATv2EPI leverages epigenetic information from enhancers, promoters, and their surrounding regions and organizes interactions into a network to comprehensively explore complex EPI regulatory patterns, including one-to-one, one-to-many, and many-to-many relationships. To avoid overfitting and ensure diverse data representation, we implemented a connectivity-based sampling method for dataset partitioning, which constructs graphs for each chromosome and assigns entire connected subgraphs to training or test sets, thereby preventing information leakage and ensuring comprehensive chromosomal representation. Results: In experiments conducted on four cell lines—NHEK, IMR90, HMEC, and K562—GATv2EPI demonstrated superior EPI recognition accuracy compared to existing similar methods, with a training time improvement of 95.29% over TransEPI. Conclusions: GATv2EPI enhances EPI prediction accuracy by capturing complex topological structure information from gene regulatory networks through graph neural networks. Additionally, our results emphasize the importance of epigenetic features surrounding enhancers and promoters in EPI prediction. Full article

(This article belongs to the Special Issue Advances and Applications of Machine Learning in Biomedical Genomics)

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12 pages, 842 KiB

Open AccessArticle

Placenta Thickness Mediates the Association Between AKIP1 Methylation in Maternal Peripheral Blood and Full-Term Small for Gestational Age Neonates

by Huimin Zhu, Min Wei, Xuemei Liu, Xiuxiu Li, Xuhua Liu and Weiqing Chen

Genes 2024, 15(12), 1510; https://doi.org/10.3390/genes15121510 - 25 Nov 2024

Abstract

Background/Objectives: A-kinase-interacting protein 1 (AKIP1) has been discovered to be a pivotal signaling adaptor in the regulation of human labor and associated with preterm birth, but its effect on fetal growth was still unclear. Meanwhile, the regulation role of DNA methylation (DNAm) on [...] Read more.

Background/Objectives: A-kinase-interacting protein 1 (AKIP1) has been discovered to be a pivotal signaling adaptor in the regulation of human labor and associated with preterm birth, but its effect on fetal growth was still unclear. Meanwhile, the regulation role of DNA methylation (DNAm) on placental and fetal development has been demonstrated. Therefore, we aimed to investigate the association of AKIP1 DNAm in maternal peripheral blood with placental development and full-term small for gestational age (FT-SGA) neonates, and to explore whether placenta mediate the association between AKIP1 DNAm and FT-SGA; Methods: This study was a case–control study including 84 FT-SGAs and 84 FT-AGAs derived from the Shenzhen Birth Cohort Study. The DNA methylation analysis of CpG in the target region of the AKIP1 gene was measured by the Sequenom MassARRAY EpiTYPER approach. Multiple-variable logistic and linear regression analyses were used to estimate the association between the DNAm of three validated CpG sites in the AKIP1 gene, placental thickness, and FT-SGA. Mediation analysis was used to examine the mediation effect of placental development on the association between the DNAm of AKIP1 and FT-SGA. Results: For every increment in standard deviation in the DNAm of CpG4 (cg00061907) at AKIP1, the risk of FT-SGA elevated by 2.01-fold (aOR = 2.01, 95%CI = 1.39~3.01), and the thickness of the placenta significantly decreased by a 0.19 standard deviation (β = −0.19, 95%CI = −0.32~ −0.06). Placental thickness mediated the 22.96% of the effect of the DNAm of CpG4 at AKIP1 on the risk of FT-SGA with statistical significance. Conclusions: The findings in the present study suggested the mediating effect of placental thickness on the association of the DNAm of AKIP1 in maternal peripheral blood and the risk of FT-SGA, providing new evidence for the mechanism of maternal epigenetics in placental and fetal development. Full article

(This article belongs to the Section Epigenomics)

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39 pages, 1985 KiB

Open AccessReview

Is the Relationship Between Cardiovascular Disease and Alzheimer’s Disease Genetic? A Scoping Review

by Anni Moore and Marylyn D. Ritchie

Genes 2024, 15(12), 1509; https://doi.org/10.3390/genes15121509 - 25 Nov 2024

Viewed by 47

Abstract

Background/Objectives: Cardiovascular disease (CVD) and Alzheimer’s disease (AD) are two diseases highly prevalent in the aging population and often co-occur. The exact relationship between the two diseases is uncertain, though epidemiological studies have demonstrated that CVDs appear to increase the risk of AD [...] Read more.

Background/Objectives: Cardiovascular disease (CVD) and Alzheimer’s disease (AD) are two diseases highly prevalent in the aging population and often co-occur. The exact relationship between the two diseases is uncertain, though epidemiological studies have demonstrated that CVDs appear to increase the risk of AD and vice versa. This scoping review aims to examine the current identified overlapping genetics between CVDs and AD at the individual gene level and at the shared pathway level. Methods: Following PRISMA-ScR guidelines for a scoping review, we searched the PubMed and Scopus databases from 1990 to October 2024 for articles that involved (1) CVDs, (2) AD, and (3) used statistical methods to parse genetic relationships. Results: Our search yielded 2918 articles, of which 274 articles passed screening and were organized into two main sections: (1) evidence of shared genetic risk; and (2) shared mechanisms. The genes APOE, PSEN1, and PSEN2 reportedly have wide effects across the AD and CVD spectrum, affecting both cardiac and brain tissues. Mechanistically, changes in three main pathways (lipid metabolism, blood pressure regulation, and the breakdown of the blood–brain barrier (BBB)) contribute to subclinical and etiological changes that promote both AD and CVD progression. However, genetic studies continue to be limited by the availability of longitudinal data and lack of cohorts that are representative of diverse populations. Conclusions: Highly penetrant familial genes simultaneously increase the risk of CVDs and AD. However, in most cases, sets of dysregulated genes within larger-scale mechanisms, like changes in lipid metabolism, blood pressure regulation, and BBB breakdown, increase the risk of both AD and CVDs and contribute to disease progression. Full article

(This article belongs to the Special Issue Genomics and Genetics of Cardiovascular Diseases)

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10 pages, 1431 KiB

Open AccessArticle

An Update of Phenotypic–Genotypic IMNEPD Cases and a Bioinformatics Analysis of the New PTRH2 Gene Variants

by Rajech Sharkia, Marie-Laure Vuillaume, Sahil Jain, Muhammad Mahajnah, Radka Stoeva, Agnès Guichet, Estelle Colin, Jérome Champ, Nicolas Derive, Arnaud Chefdor and Abdelnaser Zalan

Genes 2024, 15(12), 1508; https://doi.org/10.3390/genes15121508 - 25 Nov 2024

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Abstract

Background/Objectives: Biallelic mutations in the PTRH2 gene are associated with a rare genetic disease known as infantile-onset multisystem neurologic, endocrine, and pancreatic disease (IMNEPD). In this study, we describe a new case carrying a previously identified mutation, provide an updated analysis of the [...] Read more.

Background/Objectives: Biallelic mutations in the PTRH2 gene are associated with a rare genetic disease known as infantile-onset multisystem neurologic, endocrine, and pancreatic disease (IMNEPD). In this study, we describe a new case carrying a previously identified mutation, provide an updated analysis of the relative frequencies of the clinical features across all published cases (including the three latest studies), and perform a bioinformatics analysis of the newly identified PTRH2 protein variants from a structural perspective. Methods: Clinical examination of the patients was carried out, and genetic testing was performed using a genome sequencing strategy. A bioinformatics analysis was carried out for the newly reported mutations using PYMOL that was utilized to view the structure and analyze the mutations. Additionally, the ThermoMPNN webserver was employed to check the effect of point mutations on the overall stability of the protein. Results: Our findings indicate that motor delay, neuropathy, intellectual disability, distal weakness, hearing impairment, and ataxia are the most common symptoms, while the other clinical features fall into two frequency categories: moderately common ones and the least common ones. The bioinformatics analysis revealed that the Q85 residue is highly conserved, suggesting that mutations at this position could disrupt key signaling pathways or cellular functions. Indeed, the Q85R mutation was shown to significantly impair the stability and functionality of the protein. Conclusions: The clinical presentation of IMNEPD remains highly variable in terms of both severity and progression. Mutations at the Q85 residue have been identified in nearly 50% of reported cases, highlighting this position as a potential mutational hotspot in the PTRH2 protein. Full article

(This article belongs to the Section Bioinformatics)

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31 pages, 773 KiB

Open AccessReview

Skin and Induced Pluripotent Stem Cells as Biomarkers for Neurodegenerative Diseases

by Efstathios Rallis, Vasiliki-Sofia Grech, Kleomenis Lotsaris, Niki Tertipi, Eleni Sfyri and Vassiliki Kefala

Genes 2024, 15(12), 1507; https://doi.org/10.3390/genes15121507 - 25 Nov 2024

Viewed by 192

Abstract

As the global population ages, the rising prevalence of neurodegenerative diseases, characterized by abnormal protein aggregates, presents significant challenges for early diagnosis and disease monitoring. Identifying accessible tissue biomarkers is crucial for advancing our ability to detect and track the progression of these [...] Read more.

As the global population ages, the rising prevalence of neurodegenerative diseases, characterized by abnormal protein aggregates, presents significant challenges for early diagnosis and disease monitoring. Identifying accessible tissue biomarkers is crucial for advancing our ability to detect and track the progression of these diseases. Among the most promising biomarkers is the skin, which shares a common embryological origin with the brain and central nervous system (CNS). This biological connection positions the skin as a potential reflection of CNS pathology. Over the past decades, gene expression studies have demonstrated that key genes involved in neurodegenerative diseases are also expressed in skin tissues. Genes such as APP, PSEN1, PPA2, PINK1, LRRK2, PLCB4, MAPT, SPAST, and SPG7 are prominent in this regard. Beyond gene expression, proteins related to neurodegenerative diseases—such as α-synuclein, TAU, PARKIN, and prion protein (PrP)—have been isolated from the skin of affected individuals, underscoring the skin’s capacity to mirror neural degeneration. This non-invasive window into neurodegenerative processes is further enhanced by advances in stem cell technology, which have allowed for the generation of human-induced pluripotent stem cells (iPSCs) from patient-derived fibroblasts. These iPSCs offer a valuable model for studying disease mechanisms and developing therapeutic approaches. This review conducts a comprehensive analysis of the literature from databases such as PubMed, Google Scholar, and ResearchGate, emphasizing the unique potential of the skin as a non-invasive biomarker for neurodegenerative diseases. It explores how the skin serves as a bridge between gene expression and disease pathology in both the skin and the CNS. By leveraging this biological connection, the skin emerges as a promising model for enhancing our understanding of neurodegenerative disorders and developing innovative strategies for early detection and treatment. However, significant limitations remain, requiring further validation to establish the specificity and sensitivity of these biomarkers. Full article

(This article belongs to the Section Human Genomics and Genetic Diseases)

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13 pages, 1328 KiB

Open AccessArticle

Effects of Gene–Lifestyle Interaction on Obesity Among Students

by Emiliya S. Egorova, Kamilla K. Aseyan, Elvina R. Bikbova, Anastasia E. Zhilina, Elena V. Valeeva and Ildus I. Ahmetov

Genes 2024, 15(12), 1506; https://doi.org/10.3390/genes15121506 - 24 Nov 2024

Viewed by 260

Abstract

Background: Obesity is a global health issue influenced primarily by genetic variants and environmental factors. This study aimed to examine the relationship between genetic and lifestyle factors and their interaction with obesity risk among university students. Methods: A total of 658 students from [...] Read more.

Background: Obesity is a global health issue influenced primarily by genetic variants and environmental factors. This study aimed to examine the relationship between genetic and lifestyle factors and their interaction with obesity risk among university students. Methods: A total of 658 students from the same university participated in this study, including 531 females (mean age (SD): 21.6 (3.9) years) and 127 males (21.9 (4.6) years). Among them, 550 were classified as normal weight or underweight (456 females and 94 males), while 108 were identified as overweight or obese (75 females and 33 males). All the participants underwent anthropometric and genetic screening and completed lifestyle and sleep quality questionnaires. Results: The polygenic risk score, based on seven genetic variants (ADCY3 rs11676272, CLOCK rs1801260, GPR61 rs41279738, FTO rs1421085, RP11-775H9.2 rs1296328, SLC22A3 rs9364554, and TFAP2B rs734597), explained 8.3% (p < 0.0001) of the variance in body mass index (BMI). On the other hand, lifestyle factors—such as meal frequency, frequency of overeating, nut consumption as a snack, eating without hunger, frequency of antibiotic use in the past year, symptoms of dysbiosis, years of physical activity, sleep duration, bedtime, ground coffee consumption frequency, and evening coffee consumption time—accounted for 7.8% (p < 0.0001) of the variance in BMI. The model based on gene–environment interactions contributed 15% (p < 0.0001) to BMI variance. Conclusions: This study revealed that individuals with a higher genetic predisposition, as defined by the seven polymorphic loci, are more susceptible to becoming overweight or obese under certain lifestyle conditions. Full article

(This article belongs to the Special Issue Genetics and Epigenetics of Metabolic Diseases)

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22 pages, 6463 KiB

Open AccessArticle

Screening Key Genes Related to Nitrogen Use Efficiency in Cucumber Through Weighted Gene Co-Expression Network Analysis

by Linhao Ma, Aimin Wei, Ce Liu, Nan Liu, Yike Han, Zhengwu Chen, Ningning Wang and Shengli Du

Genes 2024, 15(12), 1505; https://doi.org/10.3390/genes15121505 - 24 Nov 2024

Viewed by 210

Abstract

Cucumber (Cucumis sativus L.) is a crucial vegetable crop, requiring significant nitrogen fertilizer inputs. However, excessive nitrogen application not only impairs growth but also poses severe environmental risks. Thus, enhancing nitrogen use efficiency (NUE) in cucumber is imperative. For the identification of [...] Read more.

Cucumber (Cucumis sativus L.) is a crucial vegetable crop, requiring significant nitrogen fertilizer inputs. However, excessive nitrogen application not only impairs growth but also poses severe environmental risks. Thus, enhancing nitrogen use efficiency (NUE) in cucumber is imperative. For the identification of genes associated with NUE in cucumber, roots of high NUE and low NUE lines were analyzed under high nitrogen conditions. Using transcriptome sequencing through WGCNA, a total of 15,180 genes were categorized into 35 co-expression modules, with 5 modules being highly correlated with NUE. Based on differential expression within the five modules and the results of GO and KEGG enrichment analyses, 25 genes were identified as potentially related to NUE. Among these, CsaV4_1G002492 (GLR22), CsaV4_2G003460 (GLR35), CsaV4_3G000307 (NRT1.1), and CsaV4_7G001709 (UPS2) were homologous to genes in Arabidopsis known to directly participate in NUE related process. These four genes were chosen as key genes for further analysis. qRT-PCR analysis revealed that CsaV4_3G000307 and CsaV4_7G001709 were more active during the early stages of the high nitrogen treatment in the high NUE line. Conversely, CsaV4_1G002492 and CsaV4_2G003460 were more active in the low NUE line. Using transcriptomic analysis, a frameshift INDEL mutation was observed in CsaV4_3G000307 in the low NUE line, which impacted the compactness of the protein structure, potentially altering its function. Analysis of protein interactions of these four key genes predicted some potential interaction networks. This research offers critical insights into the genetic factors influencing NUE in cucumber, presenting potential targets for genetic modification or breeding programs. Full article

(This article belongs to the Special Issue Genetics and Breeding of Horticulture Crops—2nd Edition)

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23 pages, 1024 KiB

Open AccessReview

Can Global DNA Methylation Be Influenced by Polymorphisms in Genes Involved in Epigenetic Mechanisms? A Review

by Naila Francis Paulo de Oliveira, Darlene Camati Persuhn and Maria Cristina Leme Godoy dos Santos

Genes 2024, 15(12), 1504; https://doi.org/10.3390/genes15121504 - 24 Nov 2024

Viewed by 391

Abstract

Background: Global methylation refers to the total methylation in the DNA and can also be inferred from the Line 1 and Alu regions, as these repeats are very abundant in the genome. The main function of DNA methylation is to control gene expression [...] Read more.

Background: Global methylation refers to the total methylation in the DNA and can also be inferred from the Line 1 and Alu regions, as these repeats are very abundant in the genome. The main function of DNA methylation is to control gene expression and is associated with both normal and pathological mechanisms. DNA methylation depends on enzymes that generate the methyl radical (e.g., methylenetetrahydrofolate reductase—MTHFR) and attach this radical to the DNA (DNA methyltransferases—DNMT). Genetic variants such as single nucleotide polymorphisms (SNP) in these genes can lead to changes in the activity or expression of MTHFR and DNMT proteins and consequently influence the DNA methylation profile. This review focuses on studies investigating inter-individual variations in the global DNA methylation profile associated with genetic polymorphisms in the MTHFR and DNMT genes. Methods: A narrative review was conducted, taking into account articles published in the last 15 years. Results: It was found that the SNPs rs1801131, rs1801133 and rs1537514 in the MTHFR gene, rs2241531, rs2228611, rs2228612, rs21124724 and the haplotype rs2288349, rs2228611, rs2228612, rs16999593 in the DNMT1 gene, rs2424909, rs998382, rs6058891, rs6058897, rs4911256, rs2889703 and rs1883729 in the DNMT3B were associated with the level of global DNA methylation, including LINE and Alu regions in different contexts. No association was found with polymorphisms in the DNMT3A gene. Conclusions: It is concluded that polymorphisms in the MTHFR and DNMT genes may influence the global DNA methylation profile in health, inflammation, tumours and mental illness. Full article

(This article belongs to the Special Issue Epigenetics in Human Development and Diseases)

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19 pages, 2754 KiB

Open AccessArticle

Rescue of Aberrant Splicing Caused by a Novel Complex Deep-intronic ABCA4 Allele

by Jordi Maggi, Silke Feil, Jiradet Gloggnitzer, Kevin Maggi, James V. M. Hanson, Samuel Koller, Christina Gerth-Kahlert and Wolfgang Berger

Genes 2024, 15(12), 1503; https://doi.org/10.3390/genes15121503 - 23 Nov 2024

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Abstract

Background/Objectives: Stargardt disease (STGD1) is an autosomal recessive disorder caused by pathogenic variants in ABCA4 that affects the retina and is characterised by progressive central vision loss. The onset of disease manifestations varies from childhood to early adulthood. Methods: Whole exome (WES), whole [...] Read more.

Background/Objectives: Stargardt disease (STGD1) is an autosomal recessive disorder caused by pathogenic variants in ABCA4 that affects the retina and is characterised by progressive central vision loss. The onset of disease manifestations varies from childhood to early adulthood. Methods: Whole exome (WES), whole gene, and whole genome sequencing (WGS) were performed for a patient with STGD1. Results: WES revealed a heterozygous pathogenic missense variant in ABCA4, but no second pathogenic variant was found. ABCA4 whole-gene sequencing, subsequent WGS, and segregation analysis identified a complex deep-intronic allele (NM_000350.2(ABCA4):c.[1555-5882C>A;1555-5784C>G]) in trans to the missense variant. Minigene assays combined with nanopore sequencing were performed to characterise this deep-intronic complex allele in more detail. Surprisingly, the reference minigene revealed the existence of two pseudoexons in intron 11 of the ABCA4 gene that are included in low-abundance (<1%) transcripts. Both pseudoexons could be confirmed in cDNA derived from wildtype retinal organoids. Despite mild splicing predictions, the variant minigene revealed that the complex deep-intronic allele substantially increased the abundance of transcripts that included the pseudoexon overlapping with the variants. Two antisense oligonucleotides (AONs) were designed to rescue the aberrant splicing events. Both AONs increased the proportion of correctly spliced transcripts, and one of them rescued correct splicing to reference levels. Conclusions: Minigene assays combined with nanopore sequencing proved instrumental in identifying low-abundance transcripts including pseudoexons from wildtype ABCA4 intron 11, one of which was substantially increased by the complex allele. Full article

(This article belongs to the Section Molecular Genetics and Genomics)

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17 pages, 7518 KiB

Open AccessArticle

CXCL10, SCGN, and H2BC5 as Potential Key Genes Regulated by HCV Infection

by Çiğdem Yıldırım, Fatih Yay, Ayfer İmre, Orçun Soysal and Hasan Çağrı Yıldırım

Genes 2024, 15(12), 1502; https://doi.org/10.3390/genes15121502 - 22 Nov 2024

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Abstract

Introduction: Hepatitis C infections are the main causes of fatal clinical conditions such as cirrhosis and HCC development, and biomarkers are needed to predict the development of these complications. Therefore, it is important to first determine which genes are deregulated in HCV-cells compared [...] Read more.

Introduction: Hepatitis C infections are the main causes of fatal clinical conditions such as cirrhosis and HCC development, and biomarkers are needed to predict the development of these complications. Therefore, it is important to first determine which genes are deregulated in HCV-cells compared to healthy individuals. In our study, we aimed to identify the genes that are commonly upregulated or downregulated in HCV-infected cells using two different databases. Material and Method: In this study, differentially expressed genes (DEGs) that were commonly upregulated or downregulated were identified using publicly available databases GSE66842 and GSE84587. Afterwards, the interactions of DEG products with each other and other proteins were examined using the STRING database. Enrichment analyses of DEGs were performed using the Enrichr-KG web tool including the Gene Ontology Biological Process, KEGG, Jensen_DISEASES and DisGeNET libraries. miRNAs targeting DEGs were detected using miRDB and TargetScanHuman8.0. Results: In HCV-infected cells, the CXCL10 expression is increased in both databases, while the SCGN and H2BC5 (HIST1H2BD) expression is decreased. No direct interaction was found among CXCL10, SCGN, H2BC5 in the top ten proteins. CXCL10 is a member of Hepatitis C and viral protein interactions with cytokine and cytokine receptor KEGG pathways. H2BC5 is a member of viral carcinogenesis KEGG pathways. Predicted overlapping miRNAs targeted by common DEGs were as follows: 59 were where CXCL10 was the estimated target, 22 where SCGN was the estimated target and 29 where H2BC5 (HIST1H2BD) was the estimated target. Conclusions: Our study identified genes that were upregulated or downregulated in HCV-infected cells in both databases and miRNAs associated with these genes, using two different databases. This study creates groundwork for future studies to investigate whether these genes can predict HCV prognosis and HCV-associated HCC development. Full article

(This article belongs to the Section Molecular Genetics and Genomics)

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13 pages, 3101 KiB

Open AccessArticle

Genetic Polymorphism of Y-Chromosome in Turkmen Population from Turkmenistan

by Maxat Zhabagin, Assel Tashkarayeva, Alizhan Bukayev, Aigul Zhunussova, Georgy Ponomarev, Saltanat Tayshanova, Albina Maxutova, Dmitry Adamov, Elena Balanovska and Zhaxylyk Sabitov

Genes 2024, 15(12), 1501; https://doi.org/10.3390/genes15121501 - 22 Nov 2024

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Abstract

This study investigates the Y-chromosome genetic diversity of the Turkmen population in Turkmenistan, analyzing 23 Y-STR loci for the first time in a sample of 100 individuals. Combined with comparative data from Turkmen populations in Afghanistan, Iran, Iraq, Russia, and Uzbekistan, this analysis [...] Read more.

This study investigates the Y-chromosome genetic diversity of the Turkmen population in Turkmenistan, analyzing 23 Y-STR loci for the first time in a sample of 100 individuals. Combined with comparative data from Turkmen populations in Afghanistan, Iran, Iraq, Russia, and Uzbekistan, this analysis offers insights into the genetic structure and relationships among Turkmen populations across regions across Central Asia and the Near East. High haplotype diversity in the Turkmen of Turkmenistan is shaped by founder effects (lineage expansions) from distinct haplogroups, with haplogroups Q and R1a predominating. Subhaplogroups Q1a and Q1b identified in Turkmenistan trace back to ancient Y-chromosome lineages from the Bronze Age. Comparative analyses, including genetic distance (RST), median-joining network, and multidimensional scaling (MDS), highlight the genetic proximity of the Turkmen in Turkmenistan to those in Afghanistan and Iran, while Iraqi Turkmen display unique characteristics, aligning with Near Eastern populations. This study underscores the Central Asian genetic affinity across most Turkmen populations. It demonstrates the value of deep-sequencing Y-chromosome data in tracing the patrilineal history of Central Asia for future studies. These findings contribute to a more comprehensive understanding of Turkmen genetic ancestry and add new data to the ongoing study of Central Asian population genetics. Full article

(This article belongs to the Special Issue The Genetic Diversification of Human Populations)

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13 pages, 532 KiB

Open AccessArticle

Targeted Transcriptome Analysis of Beef Cattle Persistently Infected with Bovine Viral Diarrhea Virus

by Morgan Adkins, Sonia Moisa, Jon Beever and Andrea Lear

Genes 2024, 15(12), 1500; https://doi.org/10.3390/genes15121500 - 22 Nov 2024

Viewed by 361

Abstract

Background: Bovine viral diarrhea virus (BVDV) is an endemic virus of North American cattle populations with significant economic and animal health impacts. While BVDV infection has a myriad of clinical manifestations, a unique and problematic outcome is the establishment of a persistently infected [...] Read more.

Background: Bovine viral diarrhea virus (BVDV) is an endemic virus of North American cattle populations with significant economic and animal health impacts. While BVDV infection has a myriad of clinical manifestations, a unique and problematic outcome is the establishment of a persistently infected (PI) animal following in utero viral infection. While it is well established that PI animals serve as a constant reservoir of BVDV, the mechanism for the maintained infection remains unknown despite multiple theories. Objective: The purpose of this study was to use transcriptome analysis to investigate the long-term immune status of adult PI cattle and offer insight into the potential mechanistic establishment of persistent BVDV infection. Methods: Peripheral blood mononuclear cells were collected from PI beef cattle (N = 6) and controls (N = 6) for targeted RNAseq analysis using 54 immune-related genes followed by pathway enrichment analysis. Results: Analysis revealed 29 differentially expressed genes (FDR < 0.05, fold change ≥ 2), representing 14 significant KEGG pathways between groups (FDR < 0.05). Transcriptome changes indicated chronic upregulation of interferon-gamma (IFNG) with an unexpected expression of related genes. Conclusions: These results provide novel insight into understanding the adult PI immune system and indicate maintained stimulation resulting from virus-mediated dysregulation. Full article

(This article belongs to the Section Animal Genetics and Genomics)

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12 pages, 14712 KiB

Open AccessBrief Report

Targeted Genetic Education in Dentistry in the Era of Genomics

by Farah Asa’ad, Anne Nørremølle, Qalbi Khan, Lena Larsson, Niels Tommerup, Nuno Vibe Hermann and Asli Silahtaroglu

Genes 2024, 15(12), 1499; https://doi.org/10.3390/genes15121499 - 22 Nov 2024

Viewed by 306

Abstract

Background: The growing body of knowledge on the human genome and its variants points towards the significance of genetic factors in oral health and disease. Since the dental curricula have historically prioritized clinically oriented subjects, this focus has resulted in insufficient coverage of [...] Read more.

Background: The growing body of knowledge on the human genome and its variants points towards the significance of genetic factors in oral health and disease. Since the dental curricula have historically prioritized clinically oriented subjects, this focus has resulted in insufficient coverage of genetics. To leverage this knowledge in patient care, dental education must equip students with an understanding of the principles of genetics. Method: We have established “Genetic Educators Network in Dentistry” (GEN-Dent) to identify common concerns regarding genetics in dental education and work for a greater emphasis on genetics in future dental programs to make sure that professionals in dentistry are well-prepared to navigate the complexities of the evolving “human genome era”. Results: Here, GEN-Dent proposes specific learning goals for medical genetics in dentistry and provides supporting teaching material addressing each learning goal. The five life-like case studies exemplify different dental conditions and introduce important concepts of genetics, inspiring other educators. Conclusions: Opportunities in Scandinavian countries can be an advantage in increasing global awareness of the importance of genetics in dentistry. The integration of genetics into dental education not only aims to improve patient care but also seeks to inspire a new generation of basic scientists with clinical backgrounds in dentistry. We expect that using life-like patient cases will significantly motivate dental students when learning medical genetics. Full article

(This article belongs to the Special Issue Genetic, Epigenetic and Environmental Factors in Dental Development and Pathologies: Genes, Interactions and Dental Development)

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15 pages, 1935 KiB

Open AccessArticle

Genomic Regions Associated with Spontaneous Abortion in Holstein Heifers

by Emaly M. Suarez, Victoria C. Kelson, Jennifer N. Kiser, Kimberly M. Davenport, Brenda M. Murdoch and Holly L. Neibergs

Genes 2024, 15(12), 1498; https://doi.org/10.3390/genes15121498 - 22 Nov 2024

Viewed by 377

Abstract

Background/Objectives: The dairy industry relies on reproductive efficiency to maintain efficient milk production. Spontaneous abortion (SA), defined as pregnancy loss between gestation days 42 and 260, occurred in 4.5% of the artificially inseminated (AI) Holstein heifers and 31.6% of the embryo transfer (ET) [...] Read more.

Background/Objectives: The dairy industry relies on reproductive efficiency to maintain efficient milk production. Spontaneous abortion (SA), defined as pregnancy loss between gestation days 42 and 260, occurred in 4.5% of the artificially inseminated (AI) Holstein heifers and 31.6% of the embryo transfer (ET) recipient Holstein heifers that received in vitro-produced frozen embryos on a single dairy farm in Idaho. Methods: A genome-wide association analysis (GWAA) was performed to identify the associations (FDR p < 0.05) with SA in heifers that were bred by AI (1351 controls that delivered at term and 63 cases that aborted) that conceived following the first insemination, as well as in 59 controls and 273 cases of ET recipient heifers pregnant from the first ET. Results: There were 216 loci and 413 positional candidate genes associated (FDR p < 0.05) with SA in the heifers bred by AI in a recessive model and no loci associated with SA in the ET recipients. Conclusions: The identification of loci associated with SA in the heifers bred by AI may be used to reduce fetal loss through genomic selection. Full article

(This article belongs to the Special Issue Functional Genomics and Breeding of Animals)

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17 pages, 1410 KiB

Open AccessArticle

Leveraging Bioinformatics and Machine Learning for Identifying Prognostic Biomarkers and Predicting Clinical Outcomes in Lung Adenocarcinoma

by Kaida Cai, Wenzhi Fu, Hanwen Liu, Xiaofang Yang, Zhengyan Wang and Xin Zhao

Genes 2024, 15(12), 1497; https://doi.org/10.3390/genes15121497 - 21 Nov 2024

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Abstract

Background/Objectives: There exist significant challenges for lung adenocarcinoma (LUAD) due to its poor prognosis and limited treatment options, particularly in the advanced stages. It is crucial to identify genetic biomarkers for improving outcome predictions and guiding personalized therapies. Methods: In this study, we [...] Read more.

Background/Objectives: There exist significant challenges for lung adenocarcinoma (LUAD) due to its poor prognosis and limited treatment options, particularly in the advanced stages. It is crucial to identify genetic biomarkers for improving outcome predictions and guiding personalized therapies. Methods: In this study, we utilize a multi-step approach that combines principled sure independence screening, penalized regression methods and information gain to identify the key genetic features of the ultra-high dimensional RNA-sequencing data from LUAD patients. We then evaluate three methods of survival analysis: the Cox model, survival tree, and random survival forests (RSFs), to compare their predictive performance. Additionally, a protein–protein interaction network is used to explore the biological significance of identified genes. Results: DKK1 and TNS4 are consistently selected as significant predictors across all feature selection methods. The Kaplan–Meier method shows that high expression levels of these genes are strongly correlated with poorer survival outcomes, suggesting their potential as prognostic biomarkers. RSF outperforms Cox and survival tree methods, showing higher AUC and C-index values. The protein–protein interaction network highlights key nodes such as VEGFC and LAMA3, which play central roles in LUAD progression. Conclusions: Our findings provide valuable insights into the genetic mechanisms of LUAD. These results contribute to the development of more accurate prognostic tools and personalized treatment strategies for LUAD. Full article

(This article belongs to the Section Bioinformatics)

15 pages, 4589 KiB

Open AccessArticle

Unraveling the Anthocyanin Regulatory Mechanisms of White Mutation in Verbena stricta by Integrative Transcriptome and Metabolome Analysis

by Shengyue Chai, Jiaming Yang, Xiaofei Zhang, Xuwen Shang and Lixin Lang

Genes 2024, 15(12), 1496; https://doi.org/10.3390/genes15121496 - 21 Nov 2024

Viewed by 330

Abstract

Background: Verbena stricta is a perennial herb of the Verbenaceae family, known for its medicinal properties, wide adaptability, and high resistance. Methods: This research investigated the metabolic pathways of flower color change by combining transcriptome and metabolomics analyses. Results: In [...] Read more.

Background: Verbena stricta is a perennial herb of the Verbenaceae family, known for its medicinal properties, wide adaptability, and high resistance. Methods: This research investigated the metabolic pathways of flower color change by combining transcriptome and metabolomics analyses. Results: In purple flowers and white variants, a total of 118 differentially accumulated metabolites (DAMs), including 20 anthocyanins, and 7627 differentially expressed genes (DEGs) were found. The downregulation of delphinidin-3-O-galactoside, delphinidin-3-O-glucoside, and delphinidin-3-O-(6″-O-p-coumaroyl) glucoside, along with the absence of petunidin and malvidin derivatives, may explain the loss of pigmentation in the white-flower mutant. Fourteen candidate genes involved in anthocyanin biosynthesis were identified, among which the expression of Flavonoid 3′, 5′-hydroxylase (F3′5′H) was significantly downregulated, notably limiting flux through the delphinidin pathway and reducing delphinidin accumulation. This limitation in upstream reactions, coupled with the multi-shunt process in downstream reactions, completely blocked the production of petunidin and malvidin. Conclusions: These findings offer new opinions on the anthocyanin metabolites and key genes responsible for the floral pigmentation in V. stricta. Additionally, the white variant provides a valuable platform for future research into the ornamental flower color of the Verbenaceae family. Full article

(This article belongs to the Special Issue 5Gs in Crop Genetic and Genomic Improvement: 2nd Edition)

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16 pages, 717 KiB

Open AccessReview

Tailoring Genomic Selection for Bos taurus indicus: A Comprehensive Review of SNP Arrays and Reference Genomes

by Adebisi R. Ogunbawo, Henrique A. Mulim, Gabriel S. Campos, Allan P. Schinckel and Hinayah Rojas de Oliveira

Genes 2024, 15(12), 1495; https://doi.org/10.3390/genes15121495 - 21 Nov 2024

Viewed by 326

Abstract

Background: Advances in SNP arrays and reference genome assemblies have significantly transformed cattle genomics, particularly for Bos taurus indicus (Zebu cattle). Many commercial SNP arrays were originally designed for Bos taurus taurus, leading to ascertainment bias and the exclusion of crucial SNPs [...] Read more.

Background: Advances in SNP arrays and reference genome assemblies have significantly transformed cattle genomics, particularly for Bos taurus indicus (Zebu cattle). Many commercial SNP arrays were originally designed for Bos taurus taurus, leading to ascertainment bias and the exclusion of crucial SNPs specific to Zebu populations. This review assesses progress in SNP array and reference genome development, with a focus on efforts tailored to Zebu populations and their impact on genomic selection and breeding efficiency. Methods: We reviewed the relevant literature on the development of SNP arrays, reference genome assemblies, and SNP genotyping techniques used for Zebu cattle. Emphasis was placed on SNP arrays specifically designed for Zebu breeds, evaluating their contributions to genomic evaluations and identifying limitations in prediction accuracy. Results: Recent advancements, such as GeneSeek’s low- and high-density SNP panels, have aimed to reduce ascertainment bias and include key SNPs for Zebu populations by providing breed-specific panels. These panels have been instrumental in identifying genomic regions associated with economically important traits in Nellore cattle. Studies show that tailored SNP arrays and breed-specific reference genomes can enhance genetic diversity assessment and improve genomic predictions, supporting more effective breeding programs for Zebu cattle. Conclusions: Improved SNP arrays and breed-specific reference genomes are crucial for accurate genomic selection in Zebu cattle. Future efforts should prioritize expanding de novo genome assemblies, reducing ascertainment bias, and developing cost-effective genotyping solutions tailored to Zebu populations. Targeted genomic tools will ultimately enable more efficient breeding practices and enhance genomic selection for economically important traits in B. t. indicus cattle. Full article

(This article belongs to the Section Animal Genetics and Genomics)

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11 pages, 3329 KiB

Open AccessArticle

Effect of IGF1 on Myogenic Proliferation and Differentiation of Bovine Skeletal Muscle Satellite Cells Through PI3K/AKT Signaling Pathway

by Xin Li, Yang Cao, Yu Liu, Wenwen Fang, Cheng Xiao, Yang Cao and Yumin Zhao

Genes 2024, 15(12), 1494; https://doi.org/10.3390/genes15121494 - 21 Nov 2024

Viewed by 290

Abstract

Background: Cultivated meat, an alternative to conventional meat, has substantial potential for alleviating environmental and ethical concerns. This method of manufacturing meat involves the isolation of skeletal muscle satellite cells (SMSCs) from donor animals, after which they proliferate in vitro and differentiate [...] Read more.

Background: Cultivated meat, an alternative to conventional meat, has substantial potential for alleviating environmental and ethical concerns. This method of manufacturing meat involves the isolation of skeletal muscle satellite cells (SMSCs) from donor animals, after which they proliferate in vitro and differentiate into primitive muscle fibers. The aim of this research was to evaluate how the insulin-like growth factor 1 (IGF1) gene regulates the myogenic differentiation of bovine skeletal muscle satellite cells (bSMSCs). Methods: bSMSCs isolated from newborn calves were cultured to the third generation in vitro and differentiated into myoblasts via the serum withdrawal method. An overexpression lentivirus and siRNA targeting the IGF1 gene were constructed and transduced into bSMSCs, which were subsequently analyzed via real-time fluorescence quantitative PCR(qRT–PCR) and Western blots. The mRNA and protein levels of the myogenic differentiation markers myosin heavy chain (MyHC) and myogenin (MyoG) were determined. Results: The results revealed that the lentivirus overexpressing the IGF1 gene significantly increased the expression of MyHC and MyoG, whereas the expression of both the MyHC and MyoG mRNAs and proteins was strongly reduced by si-IGF1. Conclusions: IGF1 positively regulates the myogenic differentiation of bSMSCs. This study provides a reference for further elucidating the molecular mechanism by which the IGF1 gene regulates the myogenic differentiation of bSMSCs via the PI3K/Akt signaling pathway and lays a foundation for establishing a regulatory network of bovine muscle growth and development. Full article

(This article belongs to the Section Animal Genetics and Genomics)

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11 pages, 1000 KiB

Open AccessArticle

Genome Insights and Identification of Sex Determination Region and Sex Markers in Argyrosomus japonicus

by Yike Liu, Wanbo Li, Dinaer Yekefenhazi, Xianfeng Yang, Qihui Zhu, Kun Ye, Fang Han and Dongdong Xu

Genes 2024, 15(12), 1493; https://doi.org/10.3390/genes15121493 - 21 Nov 2024

Viewed by 431

Abstract

Background: Argyrosomus japonicus, a member of the Sciaenidae family, is widely distributed across the sea areas near China, Japan, Australia, and South Africa. The aim of this study is to provide a high-quality genome with new technology and to understand the sex [...] Read more.

Background: Argyrosomus japonicus, a member of the Sciaenidae family, is widely distributed across the sea areas near China, Japan, Australia, and South Africa. The aim of this study is to provide a high-quality genome with new technology and to understand the sex determination mechanism of this species. Methods: We generated a high-quality chromosome-level genome for Argyrosomus japonicus using PacBio HiFi and Hi-C sequencing technologies. To map the sex determination region, we employed re-sequencing data from 38 A. japonicus and conducted genome-wide association studies (GWASs) on sex phenotypes. Results: Utilizing Hifiasm, we assembled a 708.8 Mb genome with a contig N50 length of 30 Mb. Based on Hi-C data, these contigs were organized into 24 chromosomes. The completeness of the assembly was assessed to be 99% using BUSCO, and over 98% according to Merqury. We identified a total of 174.57 Mb of repetitive elements and annotated 24,726 protein-coding genes in the genome. We mapped a 2.8 Mb sex determination region on chromosome 9, within which we found two sex-linked markers. Furthermore, we confirmed that the XX-XY sex determination system is adopted in A. japonicus. Conclusions: The findings of this study provide significant insights into genetic breeding, genome evolution research, and sex control breeding in A. japonicus. Full article

(This article belongs to the Special Issue Omic Study and Genes in Fish Sex Determination and Differentiation)

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